Ileal Transposition Surgery Decreases Fat Mass and Improves Glucose Metabolism in Diabetic GK Rats: Possible Involvement of FGF21

Yan, Kemin; Chen, Weijie; Zhu, Huijuan; Lin, Guole; Pan, Hui; Li, Naishi; Wang, Linjie; Yang, Hongbo; Liu, Meijuan; Gong, Fengying

doi:10.3389/fphys.2018.00191

Cited by 12 publications

(10 citation statements)

References 59 publications

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“…These conflicting results with RYGB is probably associated with its complicated weight-loss mechanism, including restricted gastric volume, altered intestine structure, and significant changes in gut hormone levels. Interestingly, the decrease in FGF21 level was also reported in other two forms of bariatric surgeries, namely, duodenal-jejunal omega switch (DJOS) that bypasses the entire duodenum and proximal jejunum (41), and ileal transposition (IT), a classic bariatric surgery with the transposition of a distal ileum segment to the proximal jejunum (42). All the four surgical techniques mentioned above (DJB, RYGB, DJOS, and IT) include the rearrangement of the small intestine.…”

Section: Discussionmentioning

confidence: 66%

Improved FGF21 Sensitivity and Restored FGF21 Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Rats After Duodenal-Jejunal Bypass and Sleeve Gastrectomy

Liu

Wang

et al. 2019

Front. Endocrinol.

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Objective: Bariatric surgery can profoundly improve glucose and lipid metabolism in diabetic rats. Fibroblast growth factor 21 (FGF21) is an important hormone with multiple metabolic beneficial effects. Alteration in serum FGF21 level after bariatric surgery has been reported with conflicting results. Here, we investigated the effect of bariatric surgeries on FGF21 expression and sensitivity. Methods: We performed duodenal-jejunal bypass (DJB), sleeve gastrectomy (SG) and sham surgery in diabetic rats induced by high fat diet and streptozotocin. Metabolic parameters, including body weight, food intake, glucose tolerance, and lipid profiles, were monitored. FGF21 levels in both serum and liver were measured after surgery. FGF21 signaling pathway including FGF receptor 1 (FGFR1), β-klotho (KLB), and phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) was detected in the liver and white adipose tissue (WAT). We also determined FGF21 sensitivity post-operatively by acute recombinant human FGF21 injection. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted immediately after FGF21 injection. Serum triglyceride (TG) and non-esterified fatty acid (NEFA) were measured and the mRNA levels of early growth response 1 (Egr1) and c-Fos in the liver and WAT were detected after FGF21 injection. Results: Improvements in glucose tolerance, insulin sensitivity, and lipid profiles were observed after bariatric surgeries along with ameliorated lipid metabolism in the liver and WAT. Serum and hepatic FGF21 levels decreased in both DJB and SG groups. FGFR1 and phosphorylated ERK1/2 levels increased in both DJB and SG groups 8 weeks after surgery. The expression of KLB was downregulated only in the WAT after DJB and SG. Significant alteration of OGTT and ITT were observed after acute FGF21 administration in DJB and SG groups. Serum TG and NEFA in DJB and SG groups also decreased after FGF21 administration. And increased mRNA levels of Egr1 and c-Fos were detected in the liver and WAT after DJB and SG surgeries. Conclusions: DJB and SG surgeries can downregulate hepatic expression of FGF21, restore FGF21 signaling pathway and improve FGF21 sensitivity in high-fat diet/streptozotocin-induced diabetic rats.

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Section: Discussionmentioning

confidence: 66%

Improved FGF21 Sensitivity and Restored FGF21 Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Rats After Duodenal-Jejunal Bypass and Sleeve Gastrectomy

Liu

Wang

et al. 2019

Front. Endocrinol.

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“…A portion of sWAT was fixed in 10% formalin. Histological analysis and the adipocyte size of sWAT were measured, as described previously 31 . Serum fasting blood glucose of mice was measured by routine automated laboratory methods.…”

Section: Samples Collection and Biochemical Measurementsmentioning

confidence: 99%

Safflower yellow improves insulin sensitivity in high‐fat diet‐induced obese mice by promoting peroxisome proliferator‐activated receptor‐γ2 expression in subcutaneous adipose tissue

Yan

Wang

Zhu

et al. 2020

J of Diabetes Invest

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Aims/Introduction Safflower yellow (SY) and its main component, hydroxysafflor yellow A, have been demonstrated to show anti‐obesity effects. Peroxisome proliferator‐activated receptor‐γ2 (PPARγ2) is a critical transcription factor in adipose tissue metabolism. The aim of the present study was to explore the effects of SY in high‐fat diet‐induced obese mice, and further investigate the mechanism involving PPARγ2. Methods High‐fat diet‐induced obese mice were given 120 mg/kg/day SY for 8 weeks. Glucose and insulin tolerance tests were carried out. Fat mass and serum levels of glucose and insulin were measured. The expression of insulin signaling pathway‐related genes and PPARγ2 in the adipose tissue was measured. In vitro , the effects of SY (0–500 mg/L) and hydroxysafflor yellow A (0–100 mg/L) on PPARγ2 promoter activities and PPARγ2 messenger ribonucleic acid (mRNA) levels in 3T3‐L1 preadipocytes or adipocytes were also detected. Results Safflower yellow reduced fat mass, decreased glucose levels and improved insulin sensitivity in obese mice. SY also increased the mRNA levels of insulin signaling pathway‐related genes, and increased PPARγ2 mRNA levels by 39.1% in subcutaneous adipose tissue ( P < 0.05). In vitro , SY and hydroxysafflor yellow A significantly enhanced PPARγ2 promoter activities by 1.3–2.1‐fold, and increased PPARγ2 mRNA levels by 1.2–1.6‐fold in 3T3‐L1 preadipocytes or adipocytes ( P < 0.05). Conclusions SY could reduce fat mass, decrease glucose levels and improve insulin sensitivity in high‐fat diet‐induced obese mice. The probable mechanism is to increase PPARγ2 expression by stimulating PPARγ2 promoter activities, further increasing the expression of insulin signaling pathway‐related genes in subcutaneous adipose tissue.

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“…A study by Yan et al . on GK rats also showed reduced body weight, fat mass, and food intake, improved glucose metabolism, and increased insulin sensitivity after IT procedure 46 . On the other hand, other IT studies carried out on Zucker rats 43 , 47 and UCD-T2DM rats 48 revealed no impact of IT procedure on body weight.…”

Section: Discussionmentioning

confidence: 82%

Ileal transposition helps to regulate plasma hepatokine levels in obese Zucker (Crl:ZUC(ORL)-Leprfa) rats

Stygar

Sawczyn

Dulska

et al. 2021

Sci Rep

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We studied the long-term effect of ileal transposition (IT) metabolic surgery on the hepatokines: retinol-binding protein-4 (RBP4), α-2-HS-glycoprotein (aHSG/fetuin-A), and fibroblast growth factor 21 (FGF21), C-reactive protein (CRP) plasma levels, glucose metabolism, body weight, liver histology, as well as total lipids concentration in muscle, liver, and fat tissue of obese Zucker (Crl:ZUC(ORL)-Leprfa) rats. 14 adult males were randomly submitted either to IT or SHAM (control) surgery. Pre-operative hepatokines plasma levels were not significantly different in rats submitted to IT or SHAM protocol. Three months after the procedures the plasma levels of RBP4, aHSG, FGF21, and CRP were significantly lower in IT-operated animals when compared to SHAM-operated group. Three and 12 weeks after the IT and SHAM surgery, the AUCOGTT were significantly lower than AUCOGTT before the surgery. HOMA-IR was lower in rats after IT surgery in comparison to the SHAM-operated rats. Muscle and liver total lipids concentration was reduced after the IT procedure when compared to pre-IT conditions. IT had a significant reductive impact on the body weight in comparison to SHAM surgery in the 4th, 6th, 8th, and 10th week after the surgery. We conclude that IT reduces hepatokines’ plasma concentrations, muscle and liver total lipids concentration but not the inflammatory processes in the liver of Zucker (Crl:ZUC(ORL)-Leprfa) rats.

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Ileal Transposition Surgery Decreases Fat Mass and Improves Glucose Metabolism in Diabetic GK Rats: Possible Involvement of FGF21

Cited by 12 publications

References 59 publications

Improved FGF21 Sensitivity and Restored FGF21 Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Rats After Duodenal-Jejunal Bypass and Sleeve Gastrectomy

Improved FGF21 Sensitivity and Restored FGF21 Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Rats After Duodenal-Jejunal Bypass and Sleeve Gastrectomy

Safflower yellow improves insulin sensitivity in high‐fat diet‐induced obese mice by promoting peroxisome proliferator‐activated receptor‐γ2 expression in subcutaneous adipose tissue

Ileal transposition helps to regulate plasma hepatokine levels in obese Zucker (Crl:ZUC(ORL)-Leprfa) rats

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